title: A molecular basis for the exquisite CD1d-restricted antigen specificity and functional responses of natural killer T cells.
abstract: Natural killer T (NKT) cells respond to a variety of CD1d-restricted antigens (Ags), although the basis for Ag discrimination by the NKT cell receptor (TCR) is unclear. Here we have described NKT TCR fine specificity against several closely related Ags, termed altered glycolipid ligands (AGLs), which differentially stimulate NKT cells. The structures of five ternary complexes all revealed similar docking. Acyl chain modifications did not affect the interaction, but reduced NKT cell proliferation, indicating an affect on Ag processing or presentation. Conversely, truncation of the phytosphingosine chain caused an induced fit mode of TCR binding that affected TCR affinity. Modifications in the glycosyl head group had a direct impact on the TCR interaction and associated cellular response, with ligand potency reflecting the t(1/2) life of the interaction. Accordingly, we have provided a molecular basis for understanding how modifications in AGLs can result in striking alterations in the cellular response of NKT cells.
authors.affiliation: The Protein Crystallography Unit, ARC Centre of Excellence in Structural and Functional Microbial Genomics, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Kwok S
authors.initials: KS
authors.lastname: Wun
authors.forename: Garth
authors.initials: G
authors.lastname: Cameron
authors.forename: Onisha
authors.initials: O
authors.lastname: Patel
authors.forename: Siew Siew
authors.initials: SS
authors.lastname: Pang
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Pellicci
authors.forename: Lucy C
authors.initials: LC
authors.lastname: Sullivan
authors.forename: Santosh
authors.initials: S
authors.lastname: Keshipeddy
authors.forename: Mary H
authors.initials: MH
authors.lastname: Young
authors.forename: Adam P
authors.initials: AP
authors.lastname: Uldrich
authors.forename: Meena S
authors.initials: MS
authors.lastname: Thakur
authors.forename: Stewart K
authors.initials: SK
authors.lastname: Richardson
authors.forename: Amy R
authors.initials: AR
authors.lastname: Howell
authors.forename: Petr A
authors.initials: PA
authors.lastname: Illarionov
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Brooks
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.forename: James
authors.initials: J
authors.lastname: McCluskey
authors.forename: Laurent
authors.initials: L
authors.lastname: Gapin
authors.forename: Steven A
authors.initials: SA
authors.lastname: Porcelli
authors.forename: Dale I
authors.initials: DI
authors.lastname: Godfrey
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000276:immunology*; D002240:Carbohydrate Sequence; D002460:Cell Line; D049109:Cell Proliferation; D000939:Epitopes; D006017:Glycolipids / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D008969:Molecular Sequence Data; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology*; D055607:Receptors, Natural Killer Cell / Q000276:immunology
chemical_list: D055610:Antigens, CD1d; D000939:Epitopes; D006017:Glycolipids; D055607:Receptors, Natural Killer Cell